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A single-cell resolved cell-cell communication model explains lineage commitment in hematopoiesis

Megan K. Franke, View ORCID ProfileAdam L. MacLean
doi: https://doi.org/10.1101/2021.03.31.437948
Megan K. Franke
1Department of Quantitative and Computational Biology, University of Southern California, CA
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Adam L. MacLean
1Department of Quantitative and Computational Biology, University of Southern California, CA
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  • ORCID record for Adam L. MacLean
  • For correspondence: macleana@usc.edu
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Abstract

The role of cell-cell communication in cell fate decision-making has not been well-characterized through a dynamical systems perspective. To do so, here we develop multiscale models that couple cell-cell communication with cell-internal gene regulatory network dynamics. This allows us to study the influence of external signaling on cell fate decision-making at the resolution of single cells. We study the granulocyte-monocyte vs. megakaryocyte-erythrocyte fate decision, dictated by the GATA1-PU.1 network, as an exemplary bistable cell fate system, modeling the cell-internal dynamic with ordinary differential equations and the cell-cell communication via a Poisson process. We show that, for a wide range of cell communication topologies, subtle changes in signaling can lead to dramatic changes in cell fate. We find that cell-cell coupling can explain how populations of heterogeneous cell types can arise. Analysis of intrinsic and extrinsic cell-cell communication noise demonstrates that noise alone can alter the cell fate decision-making boundaries. These results illustrate how external signals alter transcriptional dynamics, and provide insight into hematopoietic cell fate decision-making.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted April 02, 2021.
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A single-cell resolved cell-cell communication model explains lineage commitment in hematopoiesis
Megan K. Franke, Adam L. MacLean
bioRxiv 2021.03.31.437948; doi: https://doi.org/10.1101/2021.03.31.437948
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A single-cell resolved cell-cell communication model explains lineage commitment in hematopoiesis
Megan K. Franke, Adam L. MacLean
bioRxiv 2021.03.31.437948; doi: https://doi.org/10.1101/2021.03.31.437948

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